Identification
- Summary
Deflazacort is a corticosteroid used to treat Duchenne muscular dystrophy.
- Brand Names
- Emflaza
- Generic Name
- Deflazacort
- DrugBank Accession Number
- DB11921
- Background
Deflazacort, also known as Emflaza, is a corticosteroid prodrug used as an agent to manage Duchenne Muscular Dystrophy (DMD). It is marketed by Marathon Pharmaceuticals and was approved in February 2017 by the FDA.14,Label
Duchenne Muscular Dystrophy is an inherited disorder resulting from mutations of the dystrophin gene, which is important for muscle function. This disease can cause serious muscle weakness and progressive breathing and cardiovascular disability, severely impacting patient quality of life and survival.3,4,15 This disease usually manifests by muscle weakness in early childhood followed by loss of the ability to walk (ambulation) as early as age 7.4
Deflazacort delays the onset of muscle related complications resulting from DMD6, prolonging the lives of children diagnosed with this disease and exerting less harmful effects on the bone health and weight than other steroid medications.5,7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Deflazacort (DB11921)
- Weight
- Average: 441.524
Monoisotopic: 441.215137722 - Chemical Formula
- C25H31NO6
- Synonyms
- Deflazacort
- External IDs
- MDL 458
- MDL-458
Pharmacology
- Indication
Deflazacort is indicated for the treatment of Duchenne Muscular Dystrophy (DMD) in patients 2 years of age and older.Label
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Duchenne muscular dystrophy •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Deflazacort exerts anti-inflammatory activity in DMD, likely improving various symptoms, including muscle weakness and cardiorespiratory symptoms in addition to delaying their onset.6 This allows for an increased quality of life and prevents the necessity for surgical procedures, such as those for scoliosis, which is associated with DMD. Studies showed significant preservation of muscle mass in patients generally treated with 0.9 mg/kg/day of deflazacort compared to a control group. The following findings are based on clinical studies using deflazacort on a long term basis6,8:
Effects on muscle strength
At age 16, individuals treated with long-term deflazacort had 63 ± 4% score in muscle strength compared to a mean muscle strength score of 31 ± 3% for control patients6. Significant improvements in climbing stairs and rising from a supine position were also seen in patients taking deflazacort.6
Effects on ambulation
Ambulation was significantly higher by 12 years of age and 18 years of age in patients taking deflazacort when compared with the control group. The control group showed a mean loss of ambulation of 2 years sooner than with deflazacort treatment.8
Effects on cardiac function
Mean left ventricular ejection fraction (a measure of cardiac function) was higher in patients treated with deflazacort over the long term. Preservation of cardiac function was demonstrated by a mean difference in ejection fraction of about 7%, favoring study groups taking deflazacort over control groups.8
Effects on spinal alignment
Children treated with deflazacort also significantly lowered the rate and severity of scoliosis and eliminated the need for scoliosis surgery after long-term treatment.6,8
- Mechanism of action
Deflazacort is a corticosteroid prodrug with an active metabolite, 21-deflazacort, which binds to the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects on the body.1,9,10 The exact mechanism by which deflazacort exerts its therapeutic effects in patients with DMD is unknown but likely occurs via its anti-inflammatory activities.Label
Target Actions Organism UGlucocorticoid receptor agonistHumans - Absorption
Deflazacort is rapidly absorbed after oral administration with peak concentration occurring within 1-2 hours.10,Label One pharmacokinetic study determined an AUC (area under the curve) of 280 ng/ml · h.1
The bioavailability of both the oral suspension and tablet are similar.Label In clinical studies, coadministration of deflazacort crushed with food or applesauce did not affect absorption or bioavailability.Label
- Volume of distribution
One study determined the volume of distribution to be 204 ± 84 L.1
- Protein binding
The protein binding of the active metabolite of deflazacort is approximately 40%.Label,12
- Metabolism
After oral ingestion, deflazacort is deacetylated at position 21 by plasma esterases, producing the active metabolite 21-deflazacort.1,10,Label,16 21-deflazacort is then further metabolized by CYP3A4 to inactive metabolite products.Label,13 Deflazacort 21-OH metabolism is extensive. The metabolite of deflazacort-21-OH is deflazacort 6-beta-OH.13,16
Hover over products below to view reaction partners
- Route of elimination
Urinary excretion is the major route of deflazacort elimination, accounting for about about 70% of the excreted dose.1 The remainder of the dose (about 30%) is excreted in the feces1. Elimination is almost completed by 24 hours post-dose.11 21-deflazacort makes up about 18% of the eliminated drug in the urine.Label
- Half-life
- Clearance
114 ±27 L/h, according to one noncompartmental pharmacokinetic study.1
The clearance of corticosteroids is enhanced in hypothyroid patients and increased in patients with hyperthyroidism. Dosing adjustments may be considered according to thyroid status.Label A study of corticosteroid clearance was performed in patients with a creatinine clearance of 15 mL/min or less, and determined that the active metabolite of deflazacort, 21-deflazacort was similar to that in patients with normal renal clearance.Label
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The LD50 for the oral dose is 5200 mg/kg (mouse); Oral TDLO (woman): 0.12 mg/kgMSDS
A note on altered endocrine function and immunosuppression
Deflazacort, as a steroid prodrug used over a long-term period, can cause hormone imbalance leading to diseases such as Cushing's Syndrome and hypothalamic-pituitary-adrenal axis suppression. It can also predispose to infection, as it promotes immunosuppression.10 It is important to monitor for hormonal imbalance and infection and provide necessary treatment if they occur.Label
Mutagenicity/carcinogenicity
Mutagenicity assays were negative in various laboratory and in vivo assays performed on rats.Label,16 Chronic use in mice for 2 years in one study resulted in a higher rate of osteoma and osteosarcomas in mice receiving 0.06, 0.12, 0.25, 0.50, or 1.0 mg/kg of deflazacort daily.Label
Use in pregnancy
There are no sufficient data to support the administration of deflazacort during pregnancy. Corticosteroid drugs such as deflazacort should only be used during pregnancy only if the benefits of therapy outweigh the potential risks.Label,16
Use in lactation
Corticosteroids, when administered systemically, are excreted in the breastmilk. Exposure may lead to disturbances in bone development and growth and endocrine disturbances in the exposed infant.Label,16
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Deflazacort can be increased when it is combined with Abametapir. Abatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Deflazacort. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Deflazacort. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Deflazacort. Acarbose The risk or severity of hyperglycemia can be increased when Deflazacort is combined with Acarbose. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of deflazacort.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of deflazacort.
- Take with or without food. The tablets may be crushed and mixed with applesauce and consumed immediately.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Calcort (Shire) / Cortax / Decortil / Deflanil / MOAID / Xalcort (Beacon Pharmaceuticals Limited) / Zamen
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Emflaza Tablet 30 mg/1 Oral Ptc Therapeutics, Inc. 2018-09-10 Not applicable US 
Emflaza Suspension 22.75 mg/1mL Oral Marathon Pharmaceuticals, LLC 2017-02-09 2020-06-30 US Emflaza Tablet 18 mg/1 Oral Marathon Pharmaceuticals, LLC 2017-02-09 2020-06-30 US Emflaza Suspension 22.75 mg/1mL Oral Ptc Therapeutics, Inc. 2018-09-10 Not applicable US Emflaza Tablet 18 mg/1 Oral Ptc Therapeutics, Inc. 2018-09-10 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Deflazacort Tablet 18 mg/1 Oral Aurobindo Pharma Limited 2024-02-09 Not applicable US Deflazacort Tablet 36 mg/1 Oral Aurobindo Pharma Limited 2024-02-09 Not applicable US Deflazacort Tablet 6 mg/1 Oral Aurobindo Pharma Limited 2024-02-09 Not applicable US Deflazacort Tablet 30 mg/1 Oral Aurobindo Pharma Limited 2024-02-09 Not applicable US
Categories
- ATC Codes
- H02AB13 — Deflazacort
- Drug Categories
- Adrenal Cortex Hormones
- Anti-Inflammatory Agents
- Corticosteroid Hormone Receptor Agonists
- Corticosteroids
- Corticosteroids for Systemic Use
- Corticosteroids for Systemic Use, Plain
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Substrates
- Fused-Ring Compounds
- Glucocorticoids
- Hyperglycemia-Associated Agents
- Immunosuppressive Agents
- Steroids
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Pregnane steroids
- Direct Parent
- Gluco/mineralocorticoids, progestogins and derivatives
- Alternative Parents
- 20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Delta-1,4-steroids / Alpha-acyloxy ketones / Oxazolines / Secondary alcohols / Imidoesters / Cyclic ketones / Cyclic alcohols and derivatives show 9 more
- Substituents
- 11-beta-hydroxysteroid / 11-hydroxysteroid / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / Alcohol / Aliphatic heteropolycyclic compound / Alpha-acyloxy ketone / Azacycle / Carbonyl group show 24 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- KR5YZ6AE4B
- CAS number
- 14484-47-0
- InChI Key
- FBHSPRKOSMHSIF-GRMWVWQJSA-N
- InChI
- InChI=1S/C25H31NO6/c1-13-26-25(20(30)12-31-14(2)27)21(32-13)10-18-17-6-5-15-9-16(28)7-8-23(15,3)22(17)19(29)11-24(18,25)4/h7-9,17-19,21-22,29H,5-6,10-12H2,1-4H3/t17-,18-,19-,21+,22+,23-,24-,25+/m0/s1
- IUPAC Name
- 2-[(1S,2S,4R,8S,9S,11S,12S,13R)-11-hydroxy-6,9,13-trimethyl-16-oxo-5-oxa-7-azapentacyclo[10.8.0.0²,⁹.0⁴,⁸.0¹³,¹⁸]icosa-6,14,17-trien-8-yl]-2-oxoethyl acetate
- SMILES
- [H][C@@]12C[C@@]3([H])[C@]4([H])CCC5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@]([H])(O)C[C@]3(C)[C@@]1(N=C(C)O2)C(=O)COC(C)=O
References
- General References
- Mollmann H, Hochhaus G, Rohatagi S, Barth J, Derendorf H: Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone. Pharm Res. 1995 Jul;12(7):1096-100. [Article]
- Ding W, Ding L, Li WB, Pan H, Lin HD: [Pharmacokinetics of deflazacort tablets in healthy Chinese volunteers]. Yao Xue Xue Bao. 2014 Jun;49(6):921-6. [Article]
- Falzarano MS, Scotton C, Passarelli C, Ferlini A: Duchenne Muscular Dystrophy: From Diagnosis to Therapy. Molecules. 2015 Oct 7;20(10):18168-84. doi: 10.3390/molecules201018168. [Article]
- Gao QQ, McNally EM: The Dystrophin Complex: Structure, Function, and Implications for Therapy. Compr Physiol. 2015 Jul 1;5(3):1223-39. doi: 10.1002/cphy.c140048. [Article]
- Joshi N, Rajeshwari K: Deflazacort. J Postgrad Med. 2009 Oct-Dec;55(4):296-300. doi: 10.4103/0022-3859.58942. [Article]
- McAdam LC, Mayo AL, Alman BA, Biggar WD: The Canadian experience with long-term deflazacort treatment in Duchenne muscular dystrophy. Acta Myol. 2012 May;31(1):16-20. [Article]
- Ferraris JR, Pasqualini T, Legal S, Sorroche P, Galich AM, Pennisi P, Domene H, Jasper H: Effect of deflazacort versus methylprednisone on growth, body composition, lipid profile, and bone mass after renal transplantation. The Deflazacort Study Group. Pediatr Nephrol. 2000 Jul;14(7):682-8. [Article]
- Houde S, Filiatrault M, Fournier A, Dube J, D'Arcy S, Berube D, Brousseau Y, Lapierre G, Vanasse M: Deflazacort use in Duchenne muscular dystrophy: an 8-year follow-up. Pediatr Neurol. 2008 Mar;38(3):200-6. doi: 10.1016/j.pediatrneurol.2007.11.001. [Article]
- Campbell C, Jacob P: Deflazacort for the treatment of Duchenne Dystrophy: a systematic review. BMC Neurol. 2003 Sep 8;3:7. doi: 10.1186/1471-2377-3-7. Epub 2003 Sep 8. [Article]
- Parente L: Deflazacort: therapeutic index, relative potency and equivalent doses versus other corticosteroids. BMC Pharmacol Toxicol. 2017 Jan 5;18(1):1. doi: 10.1186/s40360-016-0111-8. [Article]
- Assandri A, Buniva G, Martinelli E, Perazzi A, Zerilli L: Pharmacokinetics and metabolism of deflazacort in the rat, dog, monkey and man. Adv Exp Med Biol. 1984;171:9-23. [Article]
- Nayak S, Acharjya B: Deflazacort versus other glucocorticoids: a comparison. Indian J Dermatol. 2008;53(4):167-70. doi: 10.4103/0019-5154.44786. [Article]
- Deshmukh R, Sharma L, Tekade M, Kesharwani P, Trivedi P, Tekade RK: Force degradation behavior of glucocorticoid deflazacort by UPLC: isolation, identification and characterization of degradant by FTIR, NMR and mass analysis. J Biomed Res. 2016 Mar;30(2):149-161. doi: 10.7555/JBR.30.20150074. Epub 2016 Feb 20. [Article]
- FDA approval information [Link]
- Duchenne Muscular Dystrophy organization page [Link]
- Calcort 6mg tablets, Medicines UK [Link]
- FDA Approved Drug Products: Emflaza (deflazacort) tablets [Link]
- External Links
- KEGG Drug
- D03671
- PubChem Compound
- 189821
- PubChem Substance
- 347828252
- ChemSpider
- 164861
- 22396
- ChEBI
- 135720
- ChEMBL
- CHEMBL1201891
- ZINC
- ZINC000004212809
- Wikipedia
- Deflazacort
- MSDS
- Download (24.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Prevention Impacted Third Molar Tooth 1 4 Completed Treatment Chronic Renal Diseases 1 3 Completed Treatment Duchenne Muscular Dystrophy (DMD) 1 3 Terminated Treatment Limb Girdle Muscular Dystrophy 1 3 Withdrawn Treatment Duchenne Muscular Dystrophy (DMD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 6.00 mg Tablet Oral 6.000 mg Suspension Oral 22.75 mg Tablet Oral 30 mg Suspension Oral 2275000 mg Tablet Oral 3000000 mg Tablet Oral 6 mg Suspension Oral 22.75 mg/1mL Tablet Oral 18 mg/1 Tablet Oral 30 mg/1 Tablet Oral 36 mg/1 Tablet Oral 6 mg/1 Solution / drops Oral Tablet Oral Tablet Oral 600000 mg Tablet Oral 30.000 mg Tablet Oral 30.00 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) >215 C https://www.trc-canada.com/product-detail/?D228975 water solubility 108 μg/mL https://pdfs.semanticscholar.org/1eb8/8a36cea3d298d2253b27bb1a03f829871dac.pdf logP 2.4 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208684,208685Orig1s000ClinPharmR.pdf pKa 5.52 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208684,208685Orig1s000ClinPharmR.pdf - Predicted Properties
Property Value Source Water Solubility 0.0175 mg/mL ALOGPS logP 2.56 ALOGPS logP 1.8 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 14.74 Chemaxon pKa (Strongest Basic) 0.48 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 102.26 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 117.12 m3·mol-1 Chemaxon Polarizability 46.79 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-007o-0009300000-f6dfaeb1ba93bd86229e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0007-0006900000-09c635d16cf1f755a47e Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-9002100000-c5948fa3d8e1aea7b67c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-006x-0319500000-7bcfc2ee37a444687882 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0ktf-5119000000-796843895f54ad0708bb Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-006y-0944200000-fe046a0b8cec0cd97222 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 189.3096675 predictedDarkChem Lite v0.1.0 [M-H]- 219.6684036 predictedDarkChem Lite v0.1.0 [M-H]- 206.42911 predictedDeepCCS 1.0 (2019) [M+H]+ 189.1905679 predictedDarkChem Lite v0.1.0 [M+H]+ 219.5626036 predictedDarkChem Lite v0.1.0 [M+H]+ 208.32452 predictedDeepCCS 1.0 (2019) [M+Na]+ 197.7610624 predictedDarkChem Lite v0.1.0 [M+Na]+ 215.01628 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Zinc ion binding
- Specific Function
- Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
- Gene Name
- NR3C1
- Uniprot ID
- P04150
- Uniprot Name
- Glucocorticoid receptor
- Molecular Weight
- 85658.57 Da
References
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Yu J, Petrie ID, Levy RH, Ragueneau-Majlessi I: Mechanisms and Clinical Significance of Pharmacokinetic-Based Drug-Drug Interactions with Drugs Approved by the U.S. Food and Drug Administration in 2017. Drug Metab Dispos. 2019 Feb;47(2):135-144. doi: 10.1124/dmd.118.084905. Epub 2018 Nov 15. [Article]
- Dvorak Z, Pavek P: Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462. [Article]
- Deflazacort FDA label [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Dvorak Z, Pavek P: Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462. [Article]
Drug created at October 20, 2016 21:00 / Updated at October 07, 2021 12:09